Automated MRI based pipeline for glioma segmentation and prediction of grade, IDH mutation and 1p19q co-deletion

In the WHO glioma classification guidelines grade, IDH mutation and 1p19q co-deletion play a central role as they are important markers for prognosis and optimal therapy planning. Therefore, we propose a fully automatic, MRI based, 3D pipeline for glioma segmentation and classification. The designed segmentation network was a 3D U-Net achieving an average whole tumor dice score of 90%. After segmentation, the 3D tumor ROI is extracted and fed into the multi-task classification network. The network was trained and evaluated on a large heterogeneous dataset of 628 patients, collected from The Cancer Imaging Archive and BraTS 2019 databases. Additionally, the network was validated on an independent dataset of 110 patients retrospectively acquired at the Ghent University Hospital (GUH). Classification AUC scores are 0.93, 0.94 and 0.82 on the TCIA test data and 0.94, 0.86 and 0.87 on the GUH data for grade, IDH and 1p19q status respectively

Characterizing microstructural alterations in a ratmodel of mild traumatic brain injury

1. INTRODUCTION Traumatic brain injury (TBI) is an acquired brain injury that contributes to a substantial number of deaths (mortality rate: 15 per 100 000 in Europe) and a high number of cases of permanent disability (incidence rate: 235 per 100 000 in Europe). Most of the TBI patients have mild TBI (mTBI), a condition that shows no abnormalities on conventional imaging but can result in persisting cognitive defects. Diffusion imaging is an MRI technique sensitive to diffusion of water molecules in the brain and can detect subtle changes in white matter organization. The aim of this study is to investigate whether advanced diffusion MRI scanning can be used to detect microstructural changes in a rat model of mTBI. 2. MATERIALS AND METHODS 2.1 Animal model Nine female Wistar rats weighing 250 ± 19.6 g obtained mTBI utilizing the Marmarou weight drop model [1]. In brief, in anesthetized rats a steel helmet was fixed on the skull 1/3 before and 2/3 behind bregma. The rat was positioned under a 450 g brass weight on a foam bed. The weight was dropped from a height of 1m guided through a plexiglass column. The foam bed together with the rat was rapidly removed away from the column to prevent a second injury. Rats were allowed to recover for one week. 2.2 Imaging and data analysis MRI data was acquired on a 7T MRI scanner (PharmaScan, Bruker, Ettlingen) before and 1 week after injury. T2-weighted images were acquired for anatomical reference. Multishell diffusion data was acquired with multiple directions (b=800, 1500 and 2000; 32, 46 and 64 directions, respectively). Diffusion weighted images were corrected for EPI, motion and eddy current distortions and quantitative maps were calculated for the diffusion tensor and diffusion kurtosis model in ExploreDTI [2]. Furthermore diffusion kurtosis tensor estimation was done using weighted linear least squares method and maps for white matter metrics were calculated using the model of Fieremans et al. [3]. The maps were co-registered in SPM12 with a template based on the local population and a volume-of-interest analysis was performed in the hippocampus, cingulum and corpus callosum using Amide toolbox [4]. Differences between the two time points were calculated for each map using the Wilcoxon signed-rank test in SPSS. P < 0.05 was considered significant. 3. RESULTS AND DISCUSSION The DTI and DKI metrics were not significantly different between the two time points. The axonal water fraction (AWF) was significantly increased in the cingulum, corpus callosum and hippocampus after mTBI and could be explained by axonal swelling. To verify this hypothesis, histological analysis is currently ongoing. Sections will be stained for synapses, astrocytes, neurons and myelin. References Marmarou, A. et al. A new model of diffuse brain injury in rats: Part I. J Neuroscience, 80, 291-300, 1994. Leemans, A. et al. ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data. In: 17th Annual Meeting of Intl Soc Mag Reson Med, p. 3537, Hawaii, USA, 2009 Fieremans, E. et al. White matter characterization with diffusional kurtosis imaging, Neuroimage 58(1): 177-188, 2011. Loening, AM. et al. AMIDE: A Free Software Tool for Multimodality Medical Image Analysis. Molecular Imaging, 2(3):131-137, 2003

Computer aided FCD lesion detection based on T1 MRI data

Focal cortical dysplasia (FCD) is a frequent cause of epilepsy and can be detected using brain magnetic resonance imaging (MRI). The FCD lesions in MRI images are characterized by blurring of the gray matter/white matter (GM/WM) junction, cortical thickening and hyper-intensity signal within lesional region compared with other cortical regions. However, detecting FCD lesions by means of visual inspection can be a very difficult task for radiologists because the lesions are very subtle. To assist physicians in detecting the FCD lesions more efficiently and reduce the false positive regions resulted from the existing methods, we propose an algorithm for automated FCD detection based on T1 MRI data

In vivo selection of the MDA-MB-231br/eGFP cancer cell line to obtain a clinically relevant rat model for triple negative breast cancer brain metastasis

Young triple negative breast cancer (TNBC) patients are at high risk for developing very aggressive brain metastases associated with a poor prognosis and a high mortality rate. Preclinical models that allow follow-up by magnetic resonance imaging (MRI) can contribute to the development of new therapeutic approaches for brain metastasis. To date, preclinical brain tumor research has almost exclusively relied on xenograft mouse models. Yet, rats are an ideal model for imaging of brain metastasis as their larger brain offers better relative spatial resolution compared to a mouse brain. For the development of a clinically relevant rat model for TNBC brain metastasis, the MDA-MB-231br/eGFP cancer cell line can be used. However, as a result of species-dependent extracranial features, the propensity of the MDA-MB-231br/eGFP cancer cell line to metastasize exclusively to the brain needs to be enhanced by in vivo selection. In this study, repeated sequential passages of metastatic cancer cells obtained from brain metastases in nude rats were performed. Brain metastasis formation was evaluated using preclinical MRI, while bone metastasis formation was assessed using high-resolution computed tomography (CT) and 2-deoxy-2-[F-18] fluoro-D-glucose ([F-18] FDG) positron emission tomography (PET) imaging. Our results demonstrated that the metastatic tumor burden in the rat brain (number and volume) significantly increased with increasing passage, while the metastatic tumor burden in the skeleton (i.e., number of metastasis-affected bones) significantly decreased with increasing passage. However, bone metastasis development was not reduced to a negligible amount. Consequently, despite in vivo selection, our rat model is not recommended for investigating brain metastasis as a single disease. Our findings highlight the importance of well-reasoned selection of both the preclinical model and the cancer cell line in order to obtain reliable and reproducible scientific results

Exploration of gray matter correlates of cognitive training benefit in adolescents with chronic traumatic brain injury

Sustaining a traumatic brain injury (FBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood. This study investigated gray matter plasticity following 2 months of cognitive training in young patients with TBI. Sixteen adolescents in the chronic stage of moderate-severe-TBI (9 male, mean age = 15y8m +/- 1y7m) were enrolled in a cognitive computerized training program for 8 weeks (5 times/week, 40 min/session). Pre-and post-intervention, and 6 months after completion of the training, participants underwent a comprehensive neurocognitive test-battery and anatomical Magnetic Resonance Imaging scans. We selected 9 cortical-subcortical Regions-Of-Interest associated with Executive Functioning (EF-ROIs) and 3 control regions from the Desikan-Killiany atlas. Baseline analyses showed significant decreased gray matter density in the superior frontal gyri p = 0.033, superior parietal gyri p = 0.015 and thalamus p = 0.006 in adolescents with TBI compared to age and gender matched controls. Linear mixed model analyses of longitudinal volumetric data of the EF-ROI revealed no strong evidence of training-related changes in the group with TBI. However, compared to the change over time in the control regions between post-intervention and 6 months follow-up, the change in the EF-ROIs showed a significant difference. Exploratory analyses revealed a negative correlation between the change on the Digit Symbol Substitution test and the change in volume of the putamen (r = - 0.596, p = 0.015). This preliminary study contributes to the insights of training-related plasticity mechanisms after pediatric-TBI

Multi-modal measurement of cortical thickness in brain MRI for Focal Cortical Dysplasia detection

In this work we aim to improve the detection of Focal Cortical Dysplasia on MRI images using a multimodal approach. We propose to estimate the thickness of the cortex jointly using partial volume maps of T1-weighted MPRAGE and T2- weighted FLAIR images by fitting spheres into the gray matter of the brain such that the amount of probability-weighted gray matter contained in each sphere is maximized. Results on nine patients show that the FCD lesions for all patients could be detected using the multimodal approach compared to T1 alone (FCD detected in only 7 patients) and Freesurfer (4 patients)

Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma : a preclinical F98 glioblastoma rat model study

Purpose Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model. Procedures Female Fischer rats were inoculated with +/- 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model. Results Significant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group. Conclusion Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy